Heparin Research Articles

Can nebulised heparin reduce acute lung injury in patients with SARS‑CoV‑2 requiring advanced respiratory support in Ireland: the CHARTER‑Ireland phase Ib/IIa, randomised, parallel-group, open-label study

BackgroundNebulised unfractionated heparin may attenuate COVID-19 ARDS by reducing pulmonary microvascular thrombosis, blocking SARS-CoV-2 entry into cells, and decreasing lung inflammation. COVID-19 patients with a raised d-dimer have areas of pulmonary hypoperfusion on CT perfusion scans of the lung and have increased mortality risk.MethodsThis was a phase Ib/IIa open-label multi-centre, randomised controlled trial. The study was designed to evaluate whether nebulised unfractionated heparin decreased d-dimer concentrations, with safety as a co-primary outcome.ResultsForty patients were recruited, with 20 patients into each group. Mean age was 56.6 (SD 11.5) in the heparin group and 51.3 (SD 14.7) in the standard care group, while 60% of participants were male. There was no change in d-dimers from baseline to day 10 (heparin group mean change − 316.5, [SD 1840.3] and control group mean change − 321.7 [SD 3589.4]; p = 0.996). Fourteen patients suffered at least one serious adverse event, 9 patients the Heparin group and 5 in the control group. Eight patients had one or more bleeding events, 5 in the heparin group and 3 in the control group, but were no cases of pulmonary bleeding, of severe haemorrhage or of heparin-induced thrombocytopenia. Patients receiving heparin therapy had lower PaO2/FiO2 ratios, increased oxygenation indices, and decreased ROX index profiles, up to day 10. The time to separation from respiratory support, and the time to ICU or hospital discharge was similar in both groups. There were 3 deaths in the Heparin group and 2 in the control group.ConclusionsNebulised unfractionated heparin was safe and well tolerated, but did not reduce d-dimer concentrations, and worsened oxygenation indices in patients with COVID-19 ARDS.

Perioperative Management of a Pregnant Patient With a Mechanical Heart Valve Undergoing Appendectomy: a Case Report

Introduction and importance: Managing pregnant patients with mechanical heart valves who require non-cardiac surgery presents unique challenges, particularly in balancing anticoagulation to prevent thromboembolic complications while minimizing bleeding risks. This case report discusses the perioperative management of a pregnant patient with a mechanical mitral valve undergoing emergency appendectomy. Case presentation: A 28-year-old pregnant woman at 22 weeks gestation with a history of rheumatic heart disease and a mechanical mitral valve presented with acute appendicitis. Anticoagulation therapy was shifted from warfarin to low-molecular-weight heparin (LMWH) to mitigate the risks of bleeding and teratogenicity. Intravenous unfractionated heparin (UFH) was used perioperatively to maintain adequate anticoagulation. A multidisciplinary team guided the patient’s care, and she underwent a successful laparoscopic appendectomy with stable maternal and fetal outcomes. Clinical discussion: Perioperative anticoagulation in pregnant women with mechanical heart valves is critical to avoiding valve thrombosis while minimizing the risk of bleeding. In this case, using LMWH as a bridging therapy and UFH during surgery proved effective in balancing these risks. The case underscores the importance of a coordinated multidisciplinary approach to optimize maternal and fetal outcomes during emergency surgery. Conclusion: This case highlights the complexities of managing anticoagulation in pregnant patients with mechanical valves requiring non-cardiac surgery. With appropriate anticoagulation adjustment, multidisciplinary planning, and vigilant perioperative monitoring, both maternal and fetal outcomes can be favorable in such high-risk situations.

Anticoagulation Monitoring Strategies During Extracorporeal Membrane Oxygenation (ECMO) Therapy - Differences Between Simultaneously Obtained Coagulation Tests: A Retrospective Single-Center Cohort Study.

During extracorporeal membrane oxygenation (ECMO) systemic anticoagulation with unfractionated heparin (UFH) is standard-of-care. However, there is uncertainty regarding optimal anticoagulation monitoring strategies. We retrospectively investigated venovenous and venoarterial ECMO patients at the medical ICUs at the Medical University of Graz, Austria. We analyzed the correlation and concordance of R-time in thromboelastography (TEG), activated partial thromboplastin time (aPTT), and anti-Xa activity. The proportion within target range, the association of coagulation parameters above or below target range (aPTT 54-72 s; equals 1.5-2× upper limit of normal (ULN), anti-Xa activity 0.2-0.5 U/mL, and R-time in assays without heparinase 675-900 s; equals 1.5-2× ULN) with mortality, bleeding events and thrombotic complications were investigated. We analyzed 671 clusters of simultaneously performed coagulation tests in 85 ECMO cases that fulfilled inclusion criteria. Median age of patients was 57 years and 32% were female. There were poor correlations between the three coagulation tests and the proportion of discordance was 46%. Within the target range were 21% of R-time, 15% of aPTT, and 44% of anti-Xa activity measurements. Singular and multiple bleeding events occurred in 25 and 32 patients, respectively. The most common bleeding locations were catheter and cannula insertion sites followed by pulmonary hemorrhage. In VA-ECMO, anti-Xa activity was associated (OR 1.03 [1.01-1.06], p = 0.005) and correlated with bleeding events (spearman rho 0.49, p = 0.002; point biserial 0.49, p = 0.001). aPTT level below target range was associated with reduced mortality (OR 0.98 [0.97-0.99], p = 0.024). Thrombotic events occurred in six patients with no association of coagulation tests. There was a high rate of discordance and poor correlation between aPTT, anti-Xa activity and R-time in TEG in ECMO patients. We found high rates of bleeding events and in VA-ECMO an association with elevated anti-Xa activity levels.

Correction of the effect of direct oral and parenteral anticoagulants in hemorrhagic stroke

Hemorrhagic stroke is associated with high risk of adverse outcome and follows intake of anticoagulants and antiplatelet agents in 25% of cases. The latest clinical guidelines of the Neurocritical Care Society for correction (reversal) of the effect of anticoagulants and antiplatelet agents in hemorrhagic stroke were published in 2016. In accordance with PRISMA recommendations, we reviewed the PubMed, eLibrary and UpToDate databases to a depth of 5 years and selected 48 articles. Direct oral anticoagulants are currently common. To reverse their effect, one can use specific antidotes (idarucizumab is recommended for dabigatran, andexanet alfa (not yet registered In Russia) for factor Xa inhibitors (rivaroxaban, apixaban)) and combination of prothrombin complex concentrate and tranexamic acid. Protamine sulfate is antidote for unfractionated and low molecular weight heparins. Protamine sulfate completely inactivates unfractionated heparin, but it is less effective against low molecular weight heparin. It is characterized by high probability of anaphylactic reactions, especially after repeated administrations. The effectiveness of andexanet alpha and activated factor VII for reversing the effect of low molecular weight heparin is being studied. Fondaparinux sodium is used for heparin-induced thrombocytopenia. Protamine sulfate is ineffective for reversing the effect of fondaparinux. One can use prothrombin complex concentrate and andexanet alpha, but their effectiveness is unclear. Ciraparantag is being studied in clinical trials. Apparently, ciraparantag is highly effective as an antidote for various anticoagulants. Early hemostatic therapy and reversal of anticoagulant effects in patients with hemorrhagic stroke significantly reduce the risk of adverse outcomes. This problem is being studied. Regular literature review with creation of updated clinical guidelines is needed.

Outcome and safety comparison of low-molecular-weight heparin versus unfractionated heparin for bridging anticoagulation in individuals with mechanical heart valves undergoing non-cardiac surgery: A systematic review and meta-analysis

In patients with mechanical heart valves, low-molecular-weight heparin (LMWH) and unfractionated heparin are commonly used as bridging anticoagulation therapies to reduce the risk of thromboembolic events and major adverse cardiac events; however, the efficacy and safety of these therapies remain debatable. The aim of this study was to compare the safety and outcomes of LMWH and unfractionated heparin in patients with mechanical heart valve replacement undergoing non-cardiac surgery. This systematic literature review was conducted from January to June 2023, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to search for related studies through PubMed, ScienceDirect, and Cochrane Library. Categorical variables were analyzed using a Mantel-Haenszel random-effects model, with relative risk (RR) as the effect size. Higgins I2 was used to measure the heterogeneity and publication bias was assessed through funnel plots. Out of 814 potential studies, six studies (one randomized control trial and five prospective studies) were included. The analysis revealed no significant differences in thromboembolic event or valvular thrombosis (RR: 0.61; 95%CI: 0.36–1.04; p=0.07; ꭓ2=1.96; I2=0%), all-cause mortality (RR: 0.73; 95%CI: 0.40–1.35; p=0.32; ꭓ2=0.97; I2=0%), major bleeding (RR: 0.81; 95%CI: 0.53–1.23; p=0.33; ꭓ2=4.14; I2=0%), minor bleeding (RR: 1.18; 95%CI: 0.86–1.62; p=0.31; ꭓ2=4.50; I2=11%), and thrombocytopenia (RR: 0.56; 95%CI: 0.20–1.59; p=0.27; ꭓ2=0.85; I2=0%). The study highlights that LMWH and unfractionated heparin did not differ significantly when used as bridging anticoagulant therapy for non-cardiac surgery in mechanical heart valve patients.

Analysis of the registration and manufacturing of heparin drugs in Russia

Objective. To analyze the circulation processes of heparin group drugs for 2004–2024 from the point of view of the rates of registration and localization of production of active pharmaceutical substances (APS), finished dosage forms, and prospects for implementing a full production cycle in Russia.Materials and methods. An analysis of information from 693 registry entries in the State Register of Medicines dedicated to heparin-based drugs was conducted, and a database was compiled in Microsoft Excel. Information on registered drugs was classified according to their belonging to the heparin group, the name of the APS, dosage form, date of registration, presence in the list of vital and essential drugs, country of manufacture of the APS, and finished dosage forms.Results. In accordance with the anatomical-therapeutic-chemical classification, more than 20 names of drugs were classified as heparin group drugs: unfractionated heparin, low-molecular-weight heparin, heparinoid, and antithrombin III. 95 current registration certificates (hereinafter referred to as RC) and 13 RC excluded from the State Register of Medicines were studied — a total of 108 RC. Graphs were constructed to reflect the rate of drug registration in each named group. The highest rates of registration are observed in the period from 2020 to 2024 — on average 5.25 drugs are approved per year. The years with the most active registration were 2011 (11 approved drugs), 2017 (8 approved drugs), and 2023 (9 approved drugs). The production localization of heparin drugs for 2024 is presented in the diagrams. The main country producing APS for heparin drugs is China. However, for every fifth heparin drug, the full production cycle can be performed in Russia, including the synthesis of APS.Conclusions. Information was received on the structure of the product range (95 drugs are presented in 10 dosage forms for 5 different routes of administration), rate of registration of drugs in the heparin group, and localization of production of the APS, finished dosage form. The production of APS for sodium heparin is concentrated in China. Information is known about the construction in the coming years in Russia of three production sites for the production of the APS of sodium heparin: by the Chinese company “Hebei Changshan Biochemical Pharmaceutical”, the Russian company’s “Pharmasyntez-Kama” and “Severnyj ocean”. At present, only Russian companies are declared to be suppliers of APS is 3 drugs. Heparin drugs are mainly produced in Russia (75.4 % for sodium heparin drugs and 65.1 % for low-molecular-weight heparin).

Structural Characterization and Anticoagulant Potential of Colochirus quadrangularis Fucosylated Glycosaminoglycan 5−12 Oligomers with Unusual Branches

The depolymerized products and oligosaccharide fractions from sea cucumber fucosylated glycosaminoglycans (FGs) are promising anticoagulant candidates, and more novel FG-derived oligosaccharides from low-priced sea cucumbers are expected to be obtained. This study isolated 5−12 oligomers (OF1−OF3) with unusual branches from β-eliminative depolymerized products of Colochirus quadrangularis FG (CqFG). Detailed NMR analyses showed that OF1−OF3 consisted of a chondroitin 4,6-sulfates backbone and some sulfated fucosyl branches (FucS), including monosaccharides (α-l-Fuc2S4S, α-l-Fuc3S, α-l-Fuc4S, α-l-Fuc2S3S4S, and α-l-Fuc2S) and a disaccharide D-Gal3S4S-α1,3-l-Fuc2S4S with the ratio of ~36:35:10:7:3:9, attached to the C-3 position of β-d-GlcA or its derivatives, such as α-l-Δ4,5GlcA and β-d-GlcA-ol. Unusually, α-l-Fuc3S was the main FucS branch; no α-l-Fuc3S4S branch was found, and α-l-Fuc2S3S4S and α-l-Fuc2S branches were also found in OF1–OF3. The OF2 and OF3 could strongly inhibit the intrinsic and common coagulation pathways. Intrinsic FXase is a target of OF2 and OF3 inhibiting the intrinsic coagulation pathways, and the unusual side chains may increase the intrinsic FXase inhibitory activity. OF2 and OF3 showed negligible bleeding risk, and less bleeding than heparin (HP), low-molecular-weight heparins (LMWHs), and CqFG. These findings support novel FG oligosaccharides with some unusual branches from low-priced sea cucumbers to be prepared as safer anticoagulants.

Heparinized collagen-based hydrogels for tissue engineering: physical, mechanical and biological properties.

As the main protein forming the vascular extracellular matrix, collagen has a weak antigenicity, making it an attractive candidate for coatings of vascular grafts. In order to bring antithrombotic properties to collagen for obtaining suitable blood compatibility of surfaces and further bioactive molecule carrying capacity, heparinization appears as a method of choice. Thus, in this article, pH-driven self-assembly was used to form collagen-based hydrogels with physical incorporation of heparins, especially low molecular weight heparin or unfractionated heparin at 1IU/mL and 6IU/mL. These heparinized hydrogels were evaluated for their physicochemical properties including gelation kinetic, spreading, viscoelasticity, microstructure and heparin quantification, and their biocompatibility such as cytocompatibility and their capacity to release bioactive heparins with antithrombotic properties. The loading capacity of collagen-based hydrogels was higher for unfractionated heparin (60 to 80%) than for low molecular weight heparin (20%). Interestingly, the highest concentration (6IU/mL) of heparin used to form collagen-based hydrogels resulted in the formation of a softer hydrogel owning a better spreadability compared to 1IU/mL and non heparinized collagen-based hydrogel. The 3D structure observation showed a layered formation with visible pores or spaces between the layers in all types of collagen-based hydrogels. These layers are interconnected by fibrous structures, suggesting a networked architecture. Moreover, the amount of heparin released from collagen-based hydrogel prepared with 6IU /mL was higher than from those heparinized with 1IU/mL attested by a delay in blood coagulation (activated partial thromboplastin time and thrombin time) and the abolishment of thrombin generation. Those hydrogels were also biocompatible, with low albumin adsorption and no impact on cell viability. Finally, heparin is retained in these hydrogels for at least seven days after cell seeding, providing the possibility of long-term antithrombotic properties. Thus, we succeeded in develop/obtain coatings with antithrombogenic properties, biocompatible and able to retain heparins at least seven days, making them good candidates with a great potential for the development and application of efficient blood-contacting materials.

Management of post-injury anticoagulation in the traumatic brain injury patient: A scoping review.

Traumatic brain injury (TBI) remains a leading cause of morbidity and mortality among trauma patients. The care of these patients continues to be a complex endeavor with prevention of associated complications, often requiring as much attention as that of the treatment of the primary injury. Paramount among these are venous thromboembolic events (VTE) due to their high incidence, additive effect on the risk of morbidity and mortality, and the careful balance that must be utilized in their diagnosis and treatment to prevent progression of the brain injury itself. In this review, we have synthesized the most recent major studies detailing the ideal choice of chemoprophylactic agent, the timing of initiation, and continued monitoring and management strategies through the hospital course and beyond. Additional discussion is provided for subpopulations in which management can vary significantly, including the elderly, critically ill, and obese. Ultimately, current literature supports the use and safety of low molecular weight heparin over unfractionated heparin, especially when dosed using newer assays including anti-Xa levels. The timing of prophylaxis remains important, as the risk of VTE increases with each day that prophylaxis is held. Consensus findings favor initiation within 24-72 h, in the absence of documented progression, life threatening bleeding, or need for major surgical intervention. Despite available data, there continues to be significant variability in practice patterns which we hope to address with this review.

Tunable control of Cas12 activity promotes universal and fast one-pot nucleic acid detection.

The CRISPR-based detection methods have been widely applied, yet they remain limited by the non-universal nature of one-pot diagnostic approaches. Here, we report a universal one-pot fluorescent method for the detection of epidemic pathogens, delivering results within 15-20 min. This method uses heparin sodium to precisely tunes the cis-cleavage capability of Cas12 via interference with the Cas12a-crRNA binding process, thereby generating significant fluorescence due to the accumulation of isothermal amplification products. Additionally, this universal assay accommodates both classic and suboptimal PAMs, as well as various Cas12a subtypes such as LbCas12a, AsCas12a, and AapCas12b. Such a robust method demonstrates sensitivity and specificity exceeding 95% in the detection of monkeypox pseudovirus, influenza A virus, and SARS-CoV-2 from saliva or wastewater samples, when compared with qPCR or RT-qPCR. Moreover, the cost of heparin sodium per thousand uses is $0.01 to $0.04 only. Collectively, this universal and fast one-pot approach based on heparin sodium offers potential possibilities for point-of-care testing.

P1155 Safety of Venous Thromboembolism Pharmacological Prophylaxis in Hospitalized Patients with Inflammatory Bowel Disease; A Single Center Retrospective Study (VISCOUS)

Abstract Background Hospitalization secondary to inflammatory bowel disease flare is a significant risk factor for venous thromboembolism (VTE). International guidelines recommend the use of pharmacological VTE prophylaxis; however, the risk of bleeding is unknown. We therefore aimed to evaluate the safety of pharmacological thromboprophylaxis in hospitalized patients with IBD. Methods This was a retrospective cohort study. A chart review of patients’ electronic health records with IBD hospitalized between August 2017 to December 2023 was reviewed. Our primary outcome is evaluating the safety of pharmacological VTE prophylaxis. This was investigated by examining increased bleeding risks during admission, which included worsening bloody stool frequency, drop in hemoglobin (>1g/dL from baseline) and development of hemorrhagic shock after starting VTE prophylaxis. Worsening bloody stool frequency was defined as increased bloody stool frequency >1 from baseline before starting VTE prophylaxis. Finally, any major bleeding was also considered. Results Between August 2017 and December 2023, 1045 patient encounters were reviewed. 524 patients met the study inclusion and exclusion criteria, of which 98 had missing information and 73 were duplicates and could not be included. Finally, 353 patients were included in our study. Mean age 34.7 years, 205 (58%) were female males and mean duration of hospitalization was 9 days. Majority of patients were hospitalized with acute severe ulcerative colitis (ASUC) 213 (60.3%), and 140 (39.7%) had Crohn’s disease (CD) flare. Of the total cohort, 264 (75%) patients received enoxaparin 40 mg for VTE prophylaxis, and the 89 (25%) patients received 5000 units of unfractionated heparin twice a day (figure 1). Eighteen (%5) patients had a history of VTE, and 4 female patients had VTE during admission. None of our cohort had any bleeding events including worsening bloody stool frequency, drop in hemoglobin, major bleeding and development of hemorrhagic shock after starting VTE prophylaxis up to the period patients were discharged. Conclusion we found no increased risk of gastrointestinal bleeding in patients admitted with IBD on pharmacological VTE prophylaxis. Therefore, it is important to reassure healthcare providers about the safety of pharmacological VTE prophylaxis in IBD and adopt strategies that guarantee prophylaxis is administered during hospitalization. Although that a balance should be established between the benefits and risks. References -Pleet JL, Vaughn BP, Morris JA, et al. The use of pharmacological prophylaxis against venous thromboembolism in hospitalised patients with severe active ulcerative colitis. Aliment Pharmacol Ther [Internet]. 2014;39(9):940–948. -Dawwas GK, Cuker A, Schaubel DE, et al. Effectiveness and safety of prophylactic anticoagulation among hospitalized patients with inflammatory bowel disease. Blood Adv [Internet]. 2024;8(5):1272–1280. -Kaddourah O, Numan L, Jeepalyam S, et al. Venous thromboembolism prophylaxis in inflammatory bowel disease flare-ups. Ann Gastroenterol. 2019;32(6):578–583.

Multifunctional Biological Performance of Electrospun PCL Scaffolds Formulated with Silver Sulfide Nanoparticles.

Our work describes the green synthesis of silver sulfide nanoparticles (Ag2S NPs) and their formulation into polycaprolactone fibers (PCL), aiming to improve the multifunctional biological performance of PCL membranes as scaffolds. For this purpose, an extract of rosemary (Salvia rosmarinus) was employed as a reducing agent for the Ag2S NPs, obtaining irregular NPs and clusters of 5-60 nm, with a characteristic SPR absorption at 369 nm. Ag2S was successfully incorporated into PCL fibers by electrospinning using heparin (HEP) as a stabilizer/biocompatibility agent, obtaining nanostructured fibers with a ca. 500-800 nm diameter. Different amounts of Ag2S NPs (0.05, 0.5, and 1 wt.%) enhanced the nanostructured membranes' surface polarity and mechanical performance, with a controlled ion release after 6 days submerged in PBS solution, determined by cyclic voltammetry. As a result, PCL/HEP/Ag2S scaffolds exhibit high antibacterial performance (80-90%) at early stages of contact (3 h) against E. coli and S. aureus. Also, cytotoxicity analysis demonstrated that the nanostructured membranes are biocompatible and exhibit high fibroblast cell regeneration, which is optimal for their application as scaffolds. To validate the regenerative response of PCL/HEP/Ag2S scaffolds, controlled wounds were induced in Wistar rats, presenting a favorable healing response by contact with PCL/HEP/Ag2S 1%, compared with the untreated wound. Our results indicated that nanostructured scaffolds enable the development of novel nanomaterials with multifunctional biological performance.

Carbon dots with red emission as nanoprobe for sensing of heparin in biofluids and pharmaceutical samples.

Heparin (HEP) is one of the oldest anticoagulant drugs, widely used in clinical settings, particularly in surgery and dialysis machines. Despite its long history, it remains extensively employed in medical practice. This study introduces a selective and cost-effective method for the rapid detection of HEP using red-emission carbon dots (R-CDs). These R-CDs were synthesized through a one-pot hydrothermal method, utilizing neutral red and thiourea for photostability, biocompatibility, and low cytotoxicity. Key parameters affecting the sensing process, including nanoprobe volume, pH, buffer type, and incubation time, were optimized to achieve potential assay conditions. The fluorescence intensity of the nanoprobe at 625 nm gradually decreased as the concentration of HEP increased from 60 to 240 nM. These changes in fluorescence intensity showed a linear relationship with HEP concentration within this range, achieving a limit of detection (LOD) of 5 nM. The proposed nanoprobes facilitate both quantitative and qualitative non-invasive analysis of HEP in various human biofluids, suggesting their potential for broader bioanalytical applications.

Antithrombotic therapy impact on patency and bleeding complications of arteriovenous graft placement in dialysis patients.

Background: Arteriovenous grafts (AVG) can be the only bailout solution for patients who require kidney replacement therapy but are unsuitable for arteriovenous fistula (AVF) creation. Currently, high-level evidence on the effectiveness and safety of antithrombotic therapy in AVG patients is scarce. Materials and methods: Following the PICO (patient; intervention; comparator; outcome) model and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, a data search of the English literature in PubMed, SCOPUS, Central Cochrane was conducted, until March 1st, 2023 (PROSPERO Protocol Number: CRD42023401785). Studies on humans with an AVG receiving any kind of antithrombotic medication, reporting on primary and secondary patency rates, and bleeding complications were included. Due to data heterogeneity, a descriptive report of the outcomes was undertaken. Results: Twelve studies, including 22,436 patients with end-stage renal disease (ESRD) and AVG were included, with patient recruitment spanning over a 41-year time-period (1982-2023). Antithrombotic factors included acetylsalicylic acid (ASA), clopidogrel, dipyridamole, warfarin, unfractioned heparin (UFH), and direct oral anticoagulants (DOACs). Ten studies reported on primary patency rates, and two on secondary patency rates. Primary and secondary patency rates (PPR, SPR) were reported better in four studies, similar in three and worse in one study, regarding patients receiving any kind of antiplatelet therapy. Anticoagulation therapy was not associated with increased PPR or SPR, except for one study on apixaban. Patients receiving single or combined antiplatelets versus patients receiving no treatment presented higher bleeding risk in two studies and similar bleeding risk in three studies. Anticoagulation therapy, excluding apixaban, was associated with higher bleeding risk in three studies, when compared to no anticoagulation. Conclusions: Data derived from the current literature were equivocal regarding the use of antiplatelet treatment in patients with AVG. Studies on anticoagulation therapy are confined. Randomized trials with confounder stratification remain crucial for robust long-term data.

Lemierre’s Syndrome Presenting with Multisystem Complications in a Child: A Case Report and Literature Review

Background and Clinical Significance: Lemierre’s syndrome, also known as the “forgotten disease”, is a rare clinical syndrome of septic thrombophlebitis associated with morbidity and mortality. This study reports on a 6-year-old boy diagnosed with Lemierre’s syndrome, providing an in-depth case analysis and a comprehensive review of the current literature on this uncommon condition. Case Presentation: A 6-year-old boy was admitted to the pediatric intensive care unit (PICU) with septic shock, presenting with a high-grade fever of 39.5 °C for 10 days and swelling in the left leg for one week. Additionally, he had a history of swelling in the left mandibular area for five days and a skin rash. His recent medical history was unremarkable, except for decreased activity and oral intake over the past three days. Both his neonatal and past medical histories were unremarkable. Upon admission to the PICU, a multidisciplinary team was assembled to address his condition. Following a comprehensive history, physical examination, and relevant investigations, the child was diagnosed and managed as a case of Lemierre’s syndrome—the first reported case in Saudi Arabia. Treatment included antibiotics, unfractionated heparin infusion, and analgesics. Family members were counseled on the nature, severity, and prognosis of the disease. Despite the optimal treatment given to this patient, the patient died from multiorgan failure as a complication of the disease after an eight-day stay in the PICU. Conclusions: This paper reports the main presenting features and the workup of a 6-year-old male child diagnosed and managed as a case of Lemierre’s syndrome in the Saudi Arabian context. The early recognition of the symptoms of Lemierre’s syndrome and introduction of appropriate treatment in multidisciplinary teamwork are crucial to improve the outcomes of such a life-threating syndrome.

Comparison of adverse drug reactions of heparin and its derivates in the European Economic Area based on data from EudraVigilance between 2017 and 2021.

Hemodialysis patients need long-term frequent use of parenteral anticoagulants, and the side effects need to be taken seriously. This study aimed to assess the reporting of adverse drug reactions (ADRs) following administration of unfractionated heparin (UFH), low molecular weight heparins (LMWHs), fondaparinux, and danaparoid, in relation to their usage in European Economic Area (EEA). The total number of ADRs of each anticoagulant between 2017 to 2021 was collected using data from the EudraVigilance database. The number of hemorrhages, thrombocytopenia, injection-site reaction, liver injury, hypersensitivity and bone disorder were collected, respectively. Usage of these anticoagulants was estimated using sales data from the IQVIA MIDAS database. The reporting rates of ADRs were calculated and compared using χ2-test. Between 2017 and 2021 in the EEA, the overall ADRs reporting rates per 10,000,000 standard units (SU) of UFH, enoxaparin, nadroparin, dalteparin, fondaparinux, and danaparoid were 12.3, 40.8, 23.6, 36.5, 91.4, and 430.0, respectively. There were significant differences among these drugs (χ2 = 7,239.26, p < 0.001). Specifically, hemorrhage and thrombocytopenia were reported at higher rates, ranging from 2.8 to 140.1, and 2.0 to 115.9 per 10,000,000 SU among different anticoagulants. Injection-site reactions and hypersensitivity came in second, between 0.2 - 29.0 and 0.1 - 53.1 per 10,000,000 SU, respectively. The reporting rates for liver injury and bone disorder were reported at low rates. The reporting rates of ADRs for heparin and its derivates were all very low. In comparison, the reporting rate of ADRs for danaparoid and fondaparinux was relatively high. The most commonly reported ADRs were hemorrhage, thrombocytopenia, followed by injection-site reactions and hypersensitivity.

Polycationic γ-Cyclodextrin with Amino Side Chains for a Highly Efficient Anti-Heparin Coagulant.

Multicharged cyclodextrins have attracted significant attention because of their applications in biology and pharmaceuticals. This study reports an aminoethoxy-phenyl-pyridinium-modified γ-cyclodextrin (PyA-γ-CD) as a highly efficient coagulant for heparin through multivalent interactions. The UV titration experiment is performed to obtain apparent binding constants (Kobs) between PyA-γ-CD and heparin as high as 9.85 × 106M-1. The activated partial thromboplastin time (aPTT) experiment in porcine plasma indicates that PyA-γ-CD not only exhibits nearly complete neutralization activity for unfractionated heparin (UFH), but more importantly, it also effectively neutralizes three LMWHs (dalteparin (Dalte), enoxaparin (Enoxa), and nadroparin (Nadro)) with a broader therapeutic window compared to protamine. The top neutralization activity of PyA-γ-CD for UFH, Dalte, Enoxa, and Nadro is 94%, 91%, 99%, and 85%, respectively. Interestingly, in vivo assays in mice further suggest that PyA-γ-CD significantly reverses the severe bleeding caused by heparin overdose while exhibiting remarkable biocompatibility. Therefore, PyA-γ-CD holds significant potential as a heparin antidote for clinical applications.

Utility of unfractionated sodium heparin in the prevention of disseminated intravascular coagulation

Introduction: disseminated intravascular coagulation (DIC) is a serious disease characterized by a generalized activation of blood coagulation, with sequelae ranging from thrombus formation to severe bleeding.Objective: to analyze the fundamental alternatives for the management of DIC prevention related to the use of unfractionated heparin.Method: data collection was carried out through a search in the digital databases PUBMED, SCIELO (Scientific Electronic Library Online) and GOOGLE ACADEMIC. The articles were downloaded from the aforementioned platforms, and the Zotero system was used to make the corresponding citations and pertinent references.Results: according to the results achieved, the systematic review allowed to obtain a more detailed view of the studies arising from the data search, related to DIC and the use of unfractionated heparin in its prevention. The importance of research related to this drug was highlighted to improve the understanding and treatment of DIC with the aim of reducing its morbidity and mortality.Conclusions: despite unfractionated heparin presenting significant anticoagulant effects in its clinical utility, mainly in emergency situations due to its rapid action, there are few studies available for a better understanding of the management and functionality of UFH against DIC

Severe acute pulmonary embolism in pregnancy.

Pulmonary embolism (PE) is a significant cause of morbidity and mortality in pregnancy and the puerperium. In severe cases, it causes haemodynamic instability and can lead to cardiac arrest due to obstructive shock. Patients with acute PE can be risk stratified to guide their monitoring and treatment; this article focuses on intermediate- and high-risk PE. The criteria for defining high-risk PE can be used unmodified in pregnancy. Diagnostic imaging should not be delayed due to pregnancy. Low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) can be used during pregnancy and breastfeeding, and systemic thrombolysis can be used in obstetric patients, but there are significant bleeding risks and it should be reserved for high-risk PE with hypotension and shock. Although pregnancy and the puerperium are risk factors for PE, it is important to avoid early diagnostic closure, and to consider other causes for the patient's presentation.

The Effect of Exercise on Pharmacodynamics and Pharmacokinetics of a Single Dose of Unfractionated Heparin-A Randomized, Controlled, Crossover Study.

Exercise increases blood and lymph flow in working muscles, potentially affecting the bioavailability and effect of subcutaneously administered drugs. The aim of this study was to assess the influence of a single exercise session on pharmacokinetics and pharmacodynamics of a single dose of subcutaneously administered unfractionated heparin. In a crossover design, 15 healthy males underwent four experimental days where 15,000 IU of unfractionated heparin was injected subcutaneously into the thigh of the non-dominant leg. Following the injection, one of four interventions was performed in randomized order on four separate occasions, each lasting 1 h: (1) no exercise, (2) double-legged exercise, (3) single-legged exercise with the non-dominant leg (where heparin was injected), and (4) single-legged exercise with the dominant leg. Blood was sampled during and after the interventions and analyzed for activated partial thromboplastin time (aPTT) and plasma heparin via an anti-factor Xa assay. The primary endpoint (maximum aPTT minus baseline aPTT) showed no statistically significant differences between interventions, nor did maximum minus baseline plasma heparin activities. However, after 1 h, change in aPTT was greater, following double-legged exercise compared with no exercise (mean difference 3.5 s, 95% CI 0.8-6.2) and greater after single-legged exercise with the non-dominant leg compared with the dominant (9.7 s, 3.9-15.5). Similar results were observed for plasma heparin activities. In conclusion, exercise does not affect the overall pharmacokinetics and pharmacodynamics of unfractionated heparin but tends to accelerate absorption and hence effect. The study thus underscores that physical exercise affects temporal uptake of subcutaneously administered therapy.